阿莫西林/克拉维酸钾复方制剂杂质谱的变化

Impurity Profiling Changes of Amoxicillin/Potassium Clavulanate

目的探讨阿莫西林/克拉维酸钾复方药物的杂质控制策略。方法采用HPLC,比较阿莫西林和克拉维酸钾单独存在及复方后杂质谱的变化。结果加速实验中,复方样品产生新的未知杂质,且无论是源于阿莫西林的杂质还是源于克拉维酸钾的杂质均较其单独存在时变化快。结论由β-内酰胺抗生素与β-内酰胺酶抑制剂组成的复方制剂的杂质谱,并不是其单独存在时的简单加和,新药研发中应重点探讨二者的相互作用对复方中杂质谱的影响。

OBJECTIVE To develop the impurity control strategy of amoxicillin/potassium clavulanate. METHODS The impurity profiling changes of amoxicillin plus potassium clavulanate were compared with both amoxicillin and potassium clavulanate alone by HPLC. RESULTS Not only some new impurities were found. Both the impurities produced by amoxicillin or by potassium clavulanate in the complex medicine increased more quickly than in the antibiotics alone with acceleration test. CONCLUSION The results indicated that the impurity profiling of a complex medicine composed by β-lactam antibiotics and β-lactam inhibitor was not a simple mixture of both the components alone. The research should be focused on the interaction among the components influencing upon the impurity profiling of the complex medicine.